3,385 results on '"ctdna"'
Search Results
2. French Assessment of MRD by Liquid Biopsies in PDAC Patients (FRENCH.MRD.PDAC)
- Published
- 2024
3. French Assessment of MRD by Liquid Biopsies in Colorectal With Liver Metastasis Patients (FRENCH.MRD.CRLM)
- Published
- 2024
4. Circulating tumor DNA methylation: a promising clinical tool for cancer diagnosis and management.
- Author
-
Wang, Binliang, Wang, Meng, Lin, Ya, Zhao, Jinlan, Gu, Hongcang, and Li, Xiangjuan
- Subjects
- *
DNA methylation , *EARLY detection of cancer , *METHYLATION , *CIRCULATING tumor DNA , *CANCER diagnosis , *EPIGENETICS - Abstract
Cancer continues to pose significant challenges to the medical community. Early detection, accurate molecular profiling, and adequate assessment of treatment response are critical factors in improving the quality of life and survival of cancer patients. Accumulating evidence shows that circulating tumor DNA (ctDNA) shed by tumors into the peripheral blood preserves the genetic and epigenetic information of primary tumors. Notably, DNA methylation, an essential and stable epigenetic modification, exhibits both cancer- and tissue-specific patterns. As a result, ctDNA methylation has emerged as a promising molecular marker for noninvasive testing in cancer clinics. In this review, we summarize the existing techniques for ctDNA methylation detection, describe the current research status of ctDNA methylation, and present the potential applications of ctDNA-based assays in the clinic. The insights presented in this article could serve as a roadmap for future research and clinical applications of ctDNA methylation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Circulating tumor DNA: current implementation issues and future challenges for clinical utility.
- Author
-
Hu, Qilin, Chen, Lujun, Li, Kerui, Liu, Ruotong, Sun, Lei, and Han, Tao
- Subjects
- *
CANCER relapse , *CLINICAL medicine , *NUCLEOTIDE sequencing , *TREATMENT effectiveness , *DRUG resistance , *CIRCULATING tumor DNA - Abstract
Over the past decades, liquid biopsy, especially circulating tumor DNA (ctDNA), has received tremendous attention as a noninvasive detection approach for clinical applications, including early diagnosis of cancer and relapse, real-time therapeutic efficacy monitoring, potential target selection and investigation of drug resistance mechanisms. In recent years, the application of next-generation sequencing technology combined with AI technology has significantly improved the accuracy and sensitivity of liquid biopsy, enhancing its potential in solid tumors. However, the increasing integration of such promising tests to improve therapy decision making by oncologists still has complexities and challenges. Here, we propose a conceptual framework of ctDNA technologies and clinical utilities based on bibliometrics and highlight current challenges and future directions, especially in clinical applications such as early detection, minimal residual disease detection, targeted therapy, and immunotherapy. We also discuss the necessities of developing a dynamic field of translational cancer research and rigorous clinical studies that may support therapeutic strategy decision making in the near future. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
6. Unlocking the future of cancer diagnosis – promises and challenges of ctDNA-based liquid biopsies in non-small cell lung cancer.
- Author
-
Reina, Chiara, Šabanović, Berina, Lazzari, Chiara, Gregorc, Vanesa, and Heeschen, Christopher
- Abstract
The advent of liquid biopsies has brought significant changes to the diagnosis and monitoring of non-small cell lung cancer (NSCLC), presenting both promise and challenges. Molecularly targeted drugs, capable of enhancing survival rates, are now available to around a quarter of NSCLC patients. However, to ensure their effectiveness, precision diagnosis is essential. Circulating tumor DNA (ctDNA) analysis as the most advanced liquid biopsy modality to date offers a non-invasive method for tracking genomic changes in NSCLC. The potential of ctDNA is particularly rooted in its ability to furnish comprehensive (epi-)genetic insights into the tumor, thereby aiding personalized treatment strategies. One of the key advantages of ctDNA-based liquid biopsies in NSCLC is their ability to capture tumor heterogeneity. This capability ensures a more precise depiction of the tumor's (epi-)genomic landscape compared to conventional tissue biopsies. Consequently, it facilitates the identification of (epi-)genetic alterations, enabling informed treatment decisions, disease progression monitoring, and early detection of resistance-causing mutations for timely therapeutic interventions. Here we review the current state-of-the-art in ctDNA-based liquid biopsy technologies for NSCLC, exploring their potential to revolutionize clinical practice. Key advancements in ctDNA detection methods, including PCR-based assays, next-generation sequencing (NGS), and digital PCR (dPCR), are discussed, along with their respective strengths and limitations. Additionally, the clinical utility of ctDNA analysis in guiding treatment decisions, monitoring treatment response, detecting minimal residual disease, and identifying emerging resistance mechanisms is examined. Liquid biopsy analysis bears the potential of transforming NSCLC management by enabling non-invasive monitoring of Minimal Residual Disease and providing early indicators for response to targeted treatments including immunotherapy. Furthermore, considerations regarding sample collection, processing, and data interpretation are highlighted as crucial factors influencing the reliability and reproducibility of ctDNA-based assays. Addressing these challenges will be essential for the widespread adoption of ctDNA-based liquid biopsies in routine clinical practice, ultimately paving the way toward personalized medicine and improved outcomes for patients with NSCLC. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
7. Sequential RAS mutations evaluation in cell-free DNA of patients with tissue RAS wild-type metastatic colorectal cancer: the PERSEIDA (Cohort 2) study.
- Author
-
Valladares-Ayerbes, Manuel, Safont, Maria José, González Flores, Encarnación, García-Alfonso, Pilar, Aranda, Enrique, Muñoz, Ana-Maria López, Falcó Ferrer, Esther, Cirera Nogueras, Luís, Rodríguez-Salas, Nuria, Aparicio, Jorge, Llanos Muñoz, Marta, Pimentel Cáceres, Paola Patricia, Castillo Trujillo, Oscar Alfredo, Vidal Tocino, Rosario, Salgado Fernández, Mercedes, Salud-Salvia, Antonieta, Massuti Sureda, Bartomeu, Garcia-Carbonero, Rocio, Vicente Conesa, Maria Ángeles, and Lloansí Vila, Ariadna
- Abstract
Purpose: RAS (KRAS/NRAS) mutational status on a tumor biopsy is mandatory to guide the best treatment in metastatic colorectal cancer (mCRC). Determining the RAS mutational status by tumor-tissue biopsy is essential in guiding the optimal treatment decision for mCRC. RAS mutations are negative predictive factors for the use of EGFR monoclonal antibodies. Cell-free DNA (cfDNA) analysis enables minimally invasive monitoring of tumor evolution. Methods/patients: PERSEIDA was an observational, prospective study assessing cfDNA RAS, BRAF and EGFR mutations (using Idylla™) in first-line mCRC, RAS wild-type (baseline tumor-tissue biopsy) patients (cohort 2). Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. Results: 117 patients were included (103 received panitumumab + chemotherapy as first-line treatment). At baseline, 7 (6.8%) patients had RAS mutations, 4 (3.9%) BRAF mutations and no EGFR mutations were detected (cfDNA, panitumumab + chemotherapy subpopulation [panitumumab + Ch]). The baseline RAS mutational status concordance between tissue and liquid biopsies was 94.0% (93.2%, panitumumab + Ch). At 20 weeks, only one patient in the study (included in the panitumumab + Ch) had an emerging cfDNA RAS mutation. No emerging BRAF or EGFR mutations were reported. At disease progression, 6 patients had emergent mutations not present at baseline (RAS conversion rate: 13.3% [6/45]; 15.0% [6/40], panitumumab + Ch). Conclusions: The concordance rate between liquid and solid biopsies at baseline was very high, as previously reported, while our results suggest a considerable emergence of RAS mutations during disease progression. Thus, the dynamics of the genomic landscape in ctDNA may provide relevant information for the management of mCRC patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
8. Challenges of diagnosing homologous recombination deficiencies in metastatic prostate cancer: a six-year experience from a single institution.
- Author
-
Gavira, Javier, Tapia, Jose Carlos, Romano, Alejandra, Anguera, Georgia, Aguado, María, Piedra, Aida, Bosma, Freya, Sánchez, Sofía, Martin, Cristina, Algaba, Ferran, Arce, Yolanda, Ramón y Cajal, Teresa, and Maroto, Pablo
- Abstract
Purpose: We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients. Methods: This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes. Results: 144 patients were tested (113 somatic, 21 germline, and 10 both). Technical issues prevented the analysis of 23 prostatic samples (18.7%). 12 (8.3%) patients had HRD. BRCA2 was the most frequent mutation (66.7%). Patients with HRD were younger (57.5 years). Patients with BRCA mutations had poorer survival (31.9 vs 56.3 months, p = 0.048). Conclusion: In our institution, 8.3% of the patients had HRD. Tumor tissue analysis failed in 18.7% of tests. ctDNA analysis is an alternative detection method. BRCA mutations are correlated with poor prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
9. Detection of the BRAF V600E Mutation in Circulating Free Nucleic Acids as a Biomarker of Thyroid Cancer: A Review.
- Author
-
Niedziela, Emilia, Niedziela, Łukasz, Kowalska, Aldona, and Kowalik, Artur
- Abstract
Background: Liquid biopsy is a method that could potentially improve the management of thyroid cancer (TC) by enabling the detection of circulating tumor DNA and RNA (ctDNA, ctRNA). The BRAFV600E mutation appears to be the most representative example of a biomarker in liquid biopsy, as it is the most specific mutation for TC and a target for molecular therapeutics. The aim of this review is to summarize the available data on the detection of the BRAFV600E mutation in liquid biopsy in patients with TC. Methods: A comprehensive analysis of the available literature on the detection of the BRAFV600E mutation in liquid biopsy in TC was performed. Thirty-three papers meeting the inclusion criteria were selected after full-text evaluation. Results: Eleven papers discussed correlations between BRAF mutation and clinicopathological characteristics. Nine studies tested the utility of BRAFV600E detection in the assessment of residual or recurrent disease. Seven studies investigated BRAF-mutated circulating tumor nucleic acids (ctNA) as a marker of response to targeted therapy. In seven studies the method did not detect the BRAFV600E mutation. Conclusions: This review shows the potential of BRAFV600E-mutated ctNA detection in monitoring disease progression, particularly in advanced TC. The diagnostic value of BRAFV600E-mutated ctNA detection appears to be limited to advanced TC. The choice of the molecular method (quantitative PCR [qPCR], droplet digital polymerase chain reaction [ddPCR], and next-generation sequencing [NGS]) should be made based on the turnaround time, sensitivity of the test, and the clinical indications. Despite the promising outcomes of some studies, there is a need to verify these results on larger cohorts and to unify the molecular methods. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
10. Internal Overview of Prostatic Cancer Cases and Quality of BRCA1 and BRCA2 NGS Data from the FFPE Tissue.
- Author
-
Antolini, Enrica, Filosa, Alessandra, Santoni, Matteo, Antaldi, Elena, Bartoli, Elisa, Sierchio, Lidia, Giantomassi, Federica, Mandolesi, Alessandra, and Goteri, Gaia
- Subjects
- *
SCIENTIFIC literature , *MOLECULAR biology , *PROSTATE cancer patients , *BRCA genes , *CANCER patients , *PROSTATE cancer - Abstract
Background: Comprehensive genomic profiling (CGP) has gained an important role in patients with advanced prostate cancer following the introduction of PARP inhibitors in daily clinical practice. Here, we report an overview of CGP results, specifically of BRCA1 and BRCA2 HRD-repair system genes, from patients with prostate cancer analyzed in our institution, and we compare our results with those available from more recent scientific literature. Methods: The study cohort consisted of 70 patients. Somatic DNA was extracted from Formalin-Fixed Paraffin-Embedded (FFPE) tissue using a MagCore Genomic DNA FFPE One-Step Kit for MagCore System. The DNA was quantified by EasyPGX® Real-Time qPCR and EasyPGX® Analysis Software (version 4.0.13). Tissue somatic DNA libraries were prepared with Myriapod® NGS BRCA1-2 panel-NG035 and sequenced in a Mi-Seq® System. The sequence alignment in hg19 and the variant calling were performed using Myriapod® NGS Data Analysis Software version 5.0.8 NG900-SW 5.0.8 with a software detection limit (LoD) of 95%. Variants with a coverage of 500 and VAF% ≥ 5 were evaluated. Results: Tumor tissue NGS was unsuccessful in 46/70 patients (66%). Mutations of the BRCA2 gene were detected in 4 of the samples: (1) BRCA2 ex10 c.1244A>G p.His415Arg VAF = 51.03%; (2) BRCA2 ex11 c.5946delT p.Ser1982fs VAF = 72.1%; (3) BRCA2 ex11 c.3302A>G p.His1101Arg VAF = 52.9%; and (4) BRCA2 ex11 c.3195_3198delTAAT p.Asn1066fs VAF = 51.1%. Conclusions: The results from our internal overview seem to support the data and to confirm the performance of the technical issues reported in the literature. Considering the advanced age of our patients, with 84% of men over the age of 65, the application of alternative and less invasive procedures such as liquid biopsy, could be a more suitable solution for some cases. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
11. Isoform-Level Transcriptome Analysis of Peripheral Blood Mononuclear Cells from Breast Cancer Patients Identifies a Disease-Associated RASGEF1A Isoform.
- Author
-
Čelešnik, Helena, Gorenjak, Mario, Krušič, Martina, Crnobrnja, Bojana, Sobočan, Monika, Takač, Iztok, Arko, Darja, and Potočnik, Uroš
- Abstract
Simple Summary: Peripheral blood analyses can offer a minimally invasive view into systemic immunity during cancer and can lead to the identification of biomarkers for cancer screening and therapeutic management. While a limited number of studies have reported blood transcriptome in breast cancer (BC) using RNA-seq analysis, our study is the first that aimed to identify potential BC biomarkers by analyzing transcriptome at an isoform level in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women. Our approach has led to the identification of an isoform of the RASGEF1A gene, the ENST00000374459 transcriptional variant, as a promising blood mRNA biomarker for distinguishing BC and healthy subjects. Additionally, our association analysis with clinicopathological characteristics revealed that lower ENST00000374459 expression in PBMCs of breast cancer patients was associated with higher proliferation and circulating tumor DNA (ctDNA) shedding, thereby linking expression of this isoform in blood immune cells to cancer progression and spreading. Background: Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. Methods: RNA sequencing and isoform-level bioinformatics were performed on PBMCs from 12 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Results: Transcriptional analyses showed a significant (p < 0.001) decrease in the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indicating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. Conclusions: The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since standard RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
12. The Role of ctDNA and Liquid Biopsy in the Diagnosis and Monitoring of Head and Neck Cancer: Towards Precision Medicine.
- Author
-
Nassar, Sami I., Suk, Amber, Nguyen, Shaun A., Adilbay, Dauren, Pang, John, and Nathan, Cherie-Ann O.
- Abstract
Simple Summary: Liquid biopsy's use in the field of head and neck cancer has garnered interest due to providing an efficient and insightful alternative or complement to the present standards for the diagnosis and monitoring of patients. Certain biomarkers have been associated with specific cancer diagnoses, responses to treatment, and risk of recurrence, including circulating tumor DNA. Analysis of circulating tumor DNA and viral DNA via liquid biopsy has linked certain mutations and methylation patterns to various patient outcomes across several types of head and neck cancer. The present paper has reviewed the recent literature examining liquid biopsy's clinical utility in head and neck oncology and has discussed the clinical implications of aspects of circulating tumor DNA, among other biomarkers. Recent data have shown a continued rise in the worldwide annual incidence and mortality rates of head and neck cancers. The present standard for diagnosis and monitoring for disease recurrence or progression involves clinical examination, imaging, and invasive biopsy techniques of lesions suspected of being malignant. In addition to limitations relating to cost, time, and patient discomfort, these methodologies have inherent inaccuracies for detecting recurrence. In view of these limitations, the analysis of patient bodily fluid samples via liquid biopsy proposes a cost-effective and convenient alternative, which provides insight on the biogenetic and biomolecular underpinnings of oncologic disease processes. The monitoring of biomarkers for head and neck cancer via liquid biopsy, including circulating tumor DNA, circulating tumor cells, and circulating cell-free RNA, has shown clinical utility in the screening, diagnosis, prognostication, and monitoring of patients with various forms of head and neck cancer. The present review will provide an update on the current literature examining the use of liquid biopsy in head and neck cancer care and the clinical applicability of potential biomarkers, with a focus on viral and non-viral circulating tumor DNA. Possible future avenues for research to address specific shortcomings of liquid biopsy will be discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
13. The Role of Circulating Tumor DNA in Ovarian Cancer.
- Author
-
Golara, Anna, Kozłowski, Mateusz, and Cymbaluk-Płoska, Aneta
- Abstract
Simple Summary: The diagnosis and treatment of ovarian cancer still pose many problems; so, it is important to search for effective biomarkers that will allow for the detection of changes in the early stages of the disease. There is more and more talk about the use of circulating tumor DNA in oncology as a promising biomarker and an aid in tailoring individual therapy to patients. We describe what changes we can observe in ctDNA in patients with ovarian cancer and how we can use this information in diagnosis and therapy. Ovarian cancer is the deadliest of all gynecological diseases because its diagnosis and treatment still pose many problems. Surgical excision, hormone therapy, radiation, chemotherapy, or targeted therapy for eradicating the main tumor and halting the spread of metastases are among the treatment options available to individuals with ovarian cancer, depending on the disease's stage. Tumor DNA that circulates in a patient's bodily fluids has been studied recently as a possible novel biomarker for a number of cancers, as well as a means of quantifying tumor size and evaluating the efficacy of cancer therapy. The most significant alterations that we could find in the ctDNA of ovarian cancer patients—such as chromosomal instability, somatic mutations, and methylation—are discussed in this review. Additionally, we talk about the utility of ctDNA in diagnosis, prognosis, and therapy response prediction for these patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
14. Benchmarking UMI-aware and standard variant callers for low frequency ctDNA variant detection.
- Author
-
Maruzani, Rugare, Brierley, Liam, Jorgensen, Andrea, and Fowler, Anna
- Subjects
- *
CELL-free DNA , *NUCLEOTIDE sequencing , *EARLY detection of cancer , *SENSITIVITY & specificity (Statistics) , *TUMOR classification - Abstract
Background: Circulating tumour DNA (ctDNA) is a subset of cell free DNA (cfDNA) released by tumour cells into the bloodstream. Circulating tumour DNA has shown great potential as a biomarker to inform treatment in cancer patients. Collecting ctDNA is minimally invasive and reflects the entire genetic makeup of a patient's cancer. ctDNA variants in NGS data can be difficult to distinguish from sequencing and PCR artefacts due to low abundance, particularly in the early stages of cancer. Unique Molecular Identifiers (UMIs) are short sequences ligated to the sequencing library before amplification. These sequences are useful for filtering out low frequency artefacts. The utility of ctDNA as a cancer biomarker depends on accurate detection of cancer variants. Results: In this study, we benchmarked six variant calling tools, including two UMI-aware callers for their ability to call ctDNA variants. The standard variant callers tested included Mutect2, bcftools, LoFreq and FreeBayes. The UMI-aware variant callers benchmarked were UMI-VarCal and UMIErrorCorrect. We used both datasets with known variants spiked in at low frequencies, and datasets containing ctDNA, and generated synthetic UMI sequences for these datasets. Variant callers displayed different preferences for sensitivity and specificity. Mutect2 showed high sensitivity, while returning more privately called variants than any other caller in data without synthetic UMIs – an indicator of false positive variant discovery. In data encoded with synthetic UMIs, UMI-VarCal detected fewer putative false positive variants than all other callers in synthetic datasets. Mutect2 showed a balance between high sensitivity and specificity in data encoded with synthetic UMIs. Conclusions: Our results indicate UMI-aware variant callers have potential to improve sensitivity and specificity in calling low frequency ctDNA variants over standard variant calling tools. There is a growing need for further development of UMI-aware variant calling tools if effective early detection methods for cancer using ctDNA samples are to be realised. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
15. Clinical applications of circulating biomarkers in non-small cell lung cancer.
- Author
-
Hyun-Ji Oh, Imam-Aliagan, Abdulhamid B., Yeo-Bin Kim, Hyun-Jin Kim, Izaguirre, Issac A., Sung, Chang K., and Hyungshin Yim
- Subjects
NON-small-cell lung carcinoma ,CIRCULATING tumor DNA ,CANCER stem cells ,CLINICAL medicine ,LUNG cancer - Abstract
Despite recent advances in cancer diagnostics and treatment, the mortality associated with lung cancer is still the highest in the world. Late-stage diagnosis, often accompanied by metastasis, is a major contributor to the high mortality rates, emphasizing the urgent need for reliable and readily accessible diagnostic tools that can detect biomarkers unique to lung cancer. Circulating factors, such as circulating tumor DNA and extracellular vesicles, from liquid biopsy have been recognized as diagnostic or prognostic markers in lung cancer. Numerous clinical studies are currently underway to investigate the potential of circulating tumor DNA, circulating tumor RNA, exosomes, and exosomal microRNA within the context of lung cancer. Those clinical studies aim to address the poor diagnostics and limited treatment options for lung cancer, with the ultimate goal of developing clinical markers and personalized therapies. In this review, we discuss the roles of each circulating factor, its current research status, and ongoing clinical studies of circulating factors in non-small cell lung cancer. Additionally, we discuss the circulating factors specifically found in lung cancer stem cells and examine approved diagnostic assays designed to detect circulating biomarkers in lung cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
16. A Minor Groove Binder with Significant Cytotoxicity on Human Lung Cancer Cells: The Potential of Hesperetin Functionalised Silver Nanoparticles.
- Author
-
Raj, Aparna, Thomas, Riju K., Vidya, L., Neelima, S., Aparna, V. M., and Sudarsanakumar, C.
- Abstract
Natural drug functionalised silver (Ag) nanoparticles (NPs) have gained significant interest in pharmacology related applications due to their therapeutic efficiency. We have synthesised silver nanoparticle using hesperetin as a reducing and capping agent. This work aims to discuss the relevance of the hesperetin functionalised silver nanoparticles (H-AgNPs) in the field of nano-medicine. The article primarily investigates the anticancer activity of H-AgNPs and then their interactions with calf thymus DNA (ctDNA) through spectroscopic and thermodynamic techniques. The green synthesised H-AgNPs are stable, spherical in shape and size of 10 ± 3 nm average diameter. The complex formation of H-AgNPs with ctDNA was established by UV–Visible absorption, fluorescent dye displacement assay, isothermal calorimetry and viscosity measurements. The binding constants obtained from these experiments were consistently in the order of 104 Mol−1. The melting temperature analysis and FTIR measurements confirmed that the structural alterations of ctDNA by the presence of H-AgNPs are minimal. All the thermodynamic variables and the endothermic binding nature were acquired from ITC experiments. All these experimental outcomes reveal the formation of H-AgNPs-ctDNA complex, and the results consistently verify the minor groove binding mode of H-AgNPs. The binding constant and limit of detection of 1.8 μM found from the interaction studies imply the DNA detection efficiency of H-AgNPs. The cytotoxicity of H-AgNPs against A549 and L929 cell lines were determined by in vitro MTT cell viability assay and lactate dehydrogenase (LDH) assay. The cell viability and LDH enzyme release are confirmed that the H-AgNPs has high anticancer activity. Moreover, the calculated LD50 value for H-AgNPs against lung cancer cells is 118.49 µl/ml, which is a low value comparing with the value for fibroblast cells (269.35 µl/ml). In short, the results of in vitro cytotoxicity assays revealed that the synthesised nanoparticles can be considered in applications related to cancer treatments. Also, we have found that, H-AgNPs is a minor groove binder, and having high DNA detection efficiency. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
17. Focal Update on Immunotherapy and Liver Transplantation in the Era of Transplant Oncology.
- Author
-
Abdelrahim, Maen, Esmail, Abdullah, Hibi, Taizo, and Mazzaferro, Vincenzo
- Subjects
- *
CIRCULATING tumor DNA , *IMMUNE checkpoint inhibitors , *CANCER relapse , *LIVER transplantation , *CANCER treatment - Abstract
Transplant oncology is an expanding area of cancer therapy that specifically emphasizes the use of liver transplantation (LT) as the preferred treatment for patients with manageable, but unresectable, tumors. The management and optimization of overall survival strategies, accompanied by an arguably decent quality of life, have been at the forefront of liver oncology treatment, as a plurality of all primary liver cancers are identified as either hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA), which are classified as highly aggressive malignancies and frequently remain asymptomatic until they progress to advanced stages, rendering curative procedures, such as resection, impractical. This has led to an increase in utilization of neoadjuvant interventions conducted prior to surgery, which has yielded favorable outcomes. Though this treatment modality has prompted further investigations into the efficacy of immune checkpoint inhibitors (ICPIs) as standalone treatments and in combination with locoregional treatments (LRTs) to bridge more patients into curative eligibility. This multidisciplinary methodology and treatment planning has seen multiple successful trials of immunotherapy regimes and combinate treatments, setting the groundwork for increasing eligibility through downstaging and "bridging" previously ineligible patients within stringent LT criteria. Surveillance after LT is a crucial component of transplant oncology. The emergence of circulating tumor DNA (ctDNA) has provided a novel approach to identifying the recurrence of cancer in its early stages. Recent research has focused on liquid biopsy, a technique that effectively identifies the dynamics of cancer. This is another innovation to demonstrate the rate at which transplant oncology is rapidly advancing, making the focus of care feel disorienting. Modalities of care are constantly evolving, but when a field is changing as rapidly as this one, it is imperative to reorient to the data and the needs of the patients. In this commentary, we reflect on the update's utilization of ICPIs in neoadjuvant settings as well as the updates on the utilization of liquid biopsy in post-LT follow-up surveillance. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
18. ctDNA responds to neoadjuvant treatment in locally advanced rectal cancer.
- Author
-
Bürtin, Florian, Elias, Liema, Hinz, Sebastian, Forster, Michael, Hildebrandt, Guido, Frerker, Bernd, and Bock, Felix
- Abstract
Background: Liquid biopsy is a minimally invasive procedure investigating tumor mutations. Methods: In our retrospective study, we investigated whether molecular therapy monitoring of patients receiving neoadjuvant radio(chemo)therapy on a daily routine is possible in 17 patients with locally advanced rectal cancer. Six patients received short-course radiotherapy (5 × 5 Gy) with subsequent surgery, six patients were treated according RAPIDO protocol with short-course radiotherapy followed by chemotherapy (FOLFOX4) and subsequent surgery and five patients received conventional neoadjuvant radiochemotherapy with 5-FU followed by surgery. Response was assessed by Dworak. Liquid biopsies were taken before and immediately after neoadjuvant radiotherapy to isolate and ultradeeply sequence cell free DNA with a panel of 127 genes. Somatic mutations were determined bioinformatically by comparison with normal DNA from leukocytes to distinguish them from germline variants or aging mutations. Results: In 12 patients (71%) at least one somatic mutation was detected. In 8/12 patients a decrease and in 4/12 an increase or mixed response in ctDNA was seen. Statistical correlation between ctDNA analysis and clinical response could not be seen. Conclusion: ctDNA is responding to neoadjuvant therapy and liquid biopsy is easily integrated into a daily routine. As part of translational research this protocol leaves room for further investigations. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
19. PIK3CA mutational status in tissue and plasma as a prognostic biomarker in HR+/HER2− breast cancer.
- Author
-
Terán, Eduardo, Lozano, Rebeca, Rodríguez, César A., Abad, Mar, Figuero, Luis, Muñoz, José Antonio, Cigarral, Belén, Rodrígues, Aline, Sancho, Magdalena, Gómez, M. Asunción, Morchón, Daniel, Montero, Juan Carlos, Sayagués, José María, Ludeña, M. Dolores, and Fonseca, Emilio
- Subjects
- *
METASTATIC breast cancer , *CYCLIN-dependent kinase inhibitors , *EXPOSURE therapy , *HORMONE therapy , *BREAST cancer , *HORMONE receptor positive breast cancer - Abstract
Introduction: Hotspots (HS) mutations in the PIK3CA gene may lead to poorer oncological outcomes and endocrine resistance in advanced breast cancer (BC), but their prognostic role in early‐stage disease remains controversial. The overall agreement within plasma and tissue methods has not been well explored. Our aim was to correlate tissue and plasma approaches and to analyze the prognostic impact of PIK3CA mutations (PIK3CAm) in HR+/HER2− BC. Methods: A retrospective and unicentric analysis of PIK3CA mutational status in tissue and plasma samples by Cobas®PIK3CA Mutation Kit in patients with HR+/HER2− BC. Results: We analyzed 225 samples from 161 patients with luminal BC. PIK3CA mutations were identified in 62 patients (38.5%), of which 39.6% were found in tissue and 11.8% in plasma. In advanced disease, plasma and tissue correlation rate was performed in 64 cases, with an overall agreement of 70.3%. Eighty patients were treated with CDK4/6 inhibitors + endocrine therapy. We observed a moderately worse progression‐free survival (PFS) in PIK3CAm versus wild‐type (WT) (24 m vs. 30 m; HR = 1.39, p = 0.26). A subanalysis was carried out based on exons 9 and 20, which showed a statistically poorer PFS in PIK3CAm exon 9 versus 20 population (9.7 m vs. 30.3 m; HR = 2.84; p = 0.024). Furthermore, detection of PIK3CAm in plasma was linked to a worse PFS vs PIK3CAm detection just in tissue (12.4 vs. 29.3; HR = 2.4; p = 0.08). Conclusions: Our findings suggest the PIK3CA evaluation in tissue as the diagnostic method of choice, however, additional investigations are required to improve the role of liquid biopsy in the PIK3CA assessment. PIK3CAm show worse outcomes in advanced luminal BC, especially in exon 9 mutation carriers, despite visceral involvement, prior exposure to endocrine therapy or detection of PIK3CAm in plasma, with an unclear prognosis in early‐stage disease. Nonetheless, this should be validated in a prospective cohort study. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
20. Exploring evolutionary trajectories in ovarian cancer patients by longitudinal analysis of ctDNA.
- Author
-
Kutz, Oliver, Drukewitz, Stephan, Krüger, Alexander, Aust, Daniela, William, Doreen, Oster, Sandra, Schröck, Evelin, Baretton, Gustavo, Link, Theresa, Wimberger, Pauline, and Kuhlmann, Jan Dominik
- Subjects
- *
CIRCULATING tumor DNA , *OVARIAN tumors , *OVARIAN cancer , *ABDOMINAL tumors , *CANCER patients - Abstract
We analysed whether temporal heterogeneity of ctDNA encodes evolutionary patterns in ovarian cancer. Targeted sequencing of 275 cancer-associated genes was performed in a primary tumor biopsy and in ctDNA of six longitudinal plasma samples from 15 patients, using the Illumina platform. While there was low overall concordance between the mutational spectrum of the primary tumor biopsies vs. ctDNA, TP53 variants were the most commonly shared somatic alterations. Up to three variant clusters were detected in each tumor biopsy, likely representing predominant clones of the primary tumor, most of them harbouring a TP53 variant. By tracing these clusters in ctDNA, we propose that liquid biopsy may allow to assess the contribution of ancestral clones of the tumor to relapsed abdominal masses, revealing two evolutionary patterns. In pattern#1, clusters detected in the primary tumor biopsy were likely relapse seeding clones, as they contributed a major share to ctDNA at relapse. In pattern#2, similar clusters were present in tumors and ctDNA; however, they were entirely cleared from liquid biopsy after chemotherapy and were undetectable at relapse. ctDNA private variants were present among both patterns, with some of them mirroring subclonal expansions after chemotherapy. We demonstrate that tracing the temporal heterogeneity of ctDNA, even below exome scale resolution, deciphers evolutionary trajectories in ovarian cancer. Furthermore, we describe two evolutionary patterns that may help to identify relapse seeding clones for targeted therapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
21. Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.
- Author
-
Felip, E., Cho, B.C., Gutiérrez, V., Alip, A., Besse, B., Lu, S., Spira, A.I., Girard, N., Califano, R., Gadgeel, S.M., Yang, J.C.-H., Yamamoto, S., Azuma, K., Kim, Y.J., Lee, K.-H., Danchaivijitr, P., Ferreira, C.G., Cheng, Y., Sendur, M.A.N., and Chang, G.-C.
- Subjects
- *
EPIDERMAL growth factor receptors , *CIRCULATING tumor DNA , *NON-small-cell lung carcinoma , *OSIMERTINIB , *POLYMERASE chain reaction - Abstract
Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. This analysis included patients with treatment-naive, EGFR -mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR -mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR- mutant advanced NSCLC. [Display omitted] • Amivantamab-lazertinib significantly improved PFS in patients with detectable ctDNA at baseline versus osimertinib. • Amivantamab-lazertinib significantly improved PFS in patients without ctDNA clearance at C3D1 versus osimertinib. • Amivantamab-lazertinib significantly improved PFS in patients with TP53 co-mutations versus osimertinib. • Amivantamab-lazertinib significantly improved PFS in patients with liver metastases versus osimertinib. • Eighty-nine percent of patients with analyzable ctDNA by NGS from MARIPOSA had at least one high-risk baseline feature. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
22. ctDNA whole exome sequencing in pancreatic ductal adenocarcinoma unveils organ-dependent metastatic mechanisms and identifies actionable alterations in fast progressing patients.
- Author
-
Huerta, Marisol, Martín-Arana, Jorge, Gimeno-Valiente, Francisco, Carbonell-Asins, Juan Antonio, García-Micó, Blanca, Martínez-Castedo, Belén, Robledo-Yagüe, Fabián, Camblor, Daniel G., Fleitas, Tania, García Bartolomé, Miguel, Alfaro-Cervelló, Clara, Garcés-Albir, Marina, Dorcaratto, Dimitri, Muñoz-Forner, Elena, Seguí, Víctor, Mora-Oliver, Isabel, Gambardella, Valentina, Roselló, Susana, Sabater, Luis, and Roda, Desamparados
- Abstract
Understanding progression mechanisms and developing new targeted therapies is imperative in pancreatic ductal adenocarcinoma (PDAC). In this study, 80 metastatic PDAC patients were prospectively recruited and divided into discovery (n=37) and validation (n=43) cohorts. Tumor and plasma samples taken at diagnosis were pair analyzed using whole exome sequencing (WES) in patients belonging to the discovery cohort alone. The variant allele frequency (VAF) of KRAS mutations was measured by ddPCR in plasma at baseline and response assessment in all patients. Plasma WES identified at least one pathogenic variant across the cohort, uncovering oncogenic mechanisms, DNA repair, microsatellite instability, and alterations in the TGFb pathway. Interestingly, actionable mutations were mostly found in plasma rather than tissue. Patients with shorter survival showed enrichment in cellular organization regulatory pathways. Through WES we could identify a specific molecular profile of patients with liver metastasis, which exhibited exclusive mutations in genes related to the adaptive immune response pathway, highlighting the importance of the immune system in liver metastasis development. Moreover, KRAS mutations in plasma (both at diagnosis and persistent at follow-up) correlated with shorter progression free survival (PFS). Patients presenting a reduction of over 84.75 % in KRAS VAF at response assessment had similar PFS to KRAS-negative patients. Overall, plasma WES reveals molecular profiles indicative of rapid progression, potentially actionable targets, and associations between adaptive immune response pathway alterations and liver tropism. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
23. The Importance of Predictive Biomarkers and Their Correlation with the Response to Immunotherapy in Solid Tumors—Impact on Clinical Practice.
- Author
-
Mihaila, Raluca Ioana, Gheorghe, Adelina Silvana, Zob, Daniela Luminita, and Stanculeanu, Dana Lucia
- Subjects
CIRCULATING tumor DNA ,IMMUNE checkpoint inhibitors ,TREATMENT effectiveness ,GENE expression ,GENE expression profiling - Abstract
Background/Objectives: Immunotherapy has changed the therapeutic approach for various solid tumors, especially lung tumors, malignant melanoma, renal and urogenital carcinomas, demonstrating significant antitumor activity, with tolerable safety profiles and durable responses. However, not all patients benefit from immunotherapy, underscoring the need for predictive biomarkers that can identify those most likely to respond to treatment. Methods: The integration of predictive biomarkers into clinical practice for immune checkpoint inhibitors (ICI) holds great promise for personalized cancer treatment. Programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), microsatellite instability (MSI), gene expression profiles and circulating tumor DNA (ctDNA) have shown potential in predicting ICI responses across various cancers. Results: Challenges such as standardization, validation, regulatory approval, and cost-effectiveness must be addressed to realize their full potential. Predictive biomarkers are crucial for optimizing the clinical use of ICIs in cancer therapy. Conclusions: While significant progress has been made, further research and collaboration among clinicians, researchers, and regulatory institutes are essential to overcome the challenges of clinical implementation. However, little is known about the relationship between local and systemic immune responses and the correlation with response to oncological therapies and patient survival. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
24. Liquid biopsy in breast cancer.
- Author
-
Klocker, Eva Valentina and Suppan, Christoph
- Abstract
Summary: Currently, the main clinical application of liquid biopsy (LB) in breast cancer (BC) is the circulating tumor DNA (ctDNA)-based detection of treatment targets in metastatic or advanced disease. In this short review we focus on clinically relevant applications in BC and give a brief overview of potential future uses. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
25. Molecular characterization of Chinese patients with small bowel adenocarcinoma.
- Author
-
Jin, Bryan, Lv, Bin, Yan, Zhengqing, Li, Wenshuai, Song, Huan, Cui, Haoshu, Liu, Yao, Zhong, Bin, Shen, Xin, Li, Xiao, Zhang, Bei, Chen, Shiqing, Zheng, Wanwei, Liu, Jie, Luo, Feifei, and Luo, Zhongguang
- Abstract
Purpose: Small bowel adenocarcinoma (SBA) is a rare malignancy of the gastrointestinal tract, and its unique location within the small intestine presents difficulties in obtaining tissue samples from the lesions. This limitation hinders the research and development of effective clinical treatment methods. Circulating tumor DNA (ctDNA) analysis holds promise as an alternative approach for investigating SBA and guiding treatment decisions, thereby improving the prognosis of SBA. Methods: Between January 2017 and August 2021, a total of 336 tissue or plasma samples were obtained and the corresponding mutation status in tissue or blood was evaluated with NGS. Results and conclusions: The study found that in SBA tissues, the most commonly alternated genes were TP53, KRAS, and APC, and the most frequently affected pathways were RTK–RAS–MAPK, TP53, and WNT. Notably, the RTK–RAS–MAPK pathway was identified as a potential biomarker that could be targeted for treatment. Then, we validated the gene mutation profiling of ctDNA extracted from SBA patients exhibited the same characteristics as tissue samples for the first time. Subsequently, we applied ctDNA analysis on a terminal-stage patient who had shown no response to previous chemotherapy. After detecting alterations in the RTK–RAS–MAPK pathway in the ctDNA, the patient was treated with MEK + EGFR inhibitors and achieved a tumor shrinkage rate of 76.33%. Our study utilized the largest Chinese SBA cohort to uncover the molecular characteristics of this disease, which might facilitate clinical decision making for SBA patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
26. Early evaluation of the effectiveness and cost-effectiveness of ctDNA-guided selection for adjuvant chemotherapy in stage II colon cancer.
- Author
-
Kramer, Astrid, Greuter, Marjolein J. E., Schraa, Suzanna J., Vink, Geraldine R., Phallen, Jillian, Velculescu, Victor E., Meijer, Gerrit A., van den Broek, Daan, Koopman, Miriam, Roodhart, Jeanine M. L., Fijneman, Remond J. A., Retèl, Valesca P., and Coupé, Veerle M. H.
- Abstract
Background: Current patient selection for adjuvant chemotherapy (ACT) after curative surgery for stage II colon cancer (CC) is suboptimal, causing overtreatment of high-risk patients and undertreatment of low-risk patients. Postoperative circulating tumor DNA (ctDNA) could improve patient selection for ACT. Objectives: We conducted an early model-based evaluation of the (cost-)effectiveness of ctDNA-guided selection for ACT in stage II CC in the Netherlands to assess the conditions for cost-effective implementation. Methods: A validated Markov model, simulating 1000 stage II CC patients from diagnosis to death, was supplemented with ctDNA data. Five ACT selection strategies were evaluated: the current guideline (pT4, pMMR), ctDNA-only, and three strategies that combined ctDNA status with pT4 and pMMR status in different ways. For each strategy, the costs, life years, quality-adjusted life years (QALYs), recurrences, and CC deaths were estimated. Sensitivity analyses were performed to assess the impact of the costs of ctDNA testing, strategy adherence, ctDNA as a predictive biomarker, and ctDNA test performance. Results: Model predictions showed that compared to current guidelines, the ctDNA-only strategy was less effective (+2.2% recurrences, −0.016 QALYs), while the combination strategies were more effective (−3.6% recurrences, +0.038 QALYs). The combination strategies were not cost-effective, since the incremental cost-effectiveness ratio was €67,413 per QALY, exceeding the willingness-to-pay threshold of €50,000 per QALY. Sensitivity analyses showed that the combination strategies would be cost-effective if the ctDNA test costs were lower than €1500, or if ctDNA status was predictive of treatment response, or if the ctDNA test performance improved substantially. Conclusion: Adding ctDNA to current high-risk clinicopathological features (pT4 and pMMR) can improve patient selection for ACT and can also potentially be cost-effective. Future studies should investigate the predictive value of post-surgery ctDNA status to accurately evaluate the cost-effectiveness of ctDNA testing for ACT decisions in stage II CC. Plain language summary: Effectiveness and cost-effectiveness of circulating tumour DNA-guided selection for adjuvant chemotherapy in patients with stage II colon cancer Most patients with stage II colon cancer (CC) are cured by surgery. Therefore, guidelines recommend to only offer adjuvant chemotherapy to patients who have a tumor with high-risk features. However, current selection is suboptimal, leading to recurrence of cancer in 13% of low-risk patients and unnecessary administration of chemotherapy in some high-risk patients. Previous studies indicate that a biomarker, so-called circulating tumour DNA (ctDNA), could improve the selection of high-risk patients for adjuvant chemotherapy, as patients who have detectable ctDNA in their blood after surgery are likely to develop a recurrence. Despite its potential, implementation is still pending. Our study assessed the long-term effectiveness and costs associated with various ctDNA-guided strategies for selecting high-risk patients for adjuvant chemotherapy in stage II CC. We used an health-economic model to simulate a cohort of 1000 Dutch patients with stage II CC from diagnosis to death. Next, we compared the health outcomes and costs of the ctDNA-guided strategies to those when selection is based on the Dutch guideline. We found that a combination of the Dutch guideline and ctDNA was the most effective strategy, but not cost-effective. Additional analyses showed that ctDNA-guided selection were cost-effective if the costs of the ctDNA test were below 1500 euros, if the ctDNA test performed significantly better, or if patients with detectable ctDNA responded better to chemotherapy. Thus, while post-surgery ctDNA status is a good indicator for recurrence risk, specific criteria related to ctDNA test performance and costs, in addition to combining ctDNA with current high-risk features, should be met to achieve cost-effective implementation. Looking ahead, future studies should explore how patients with detectable ctDNA respond to chemotherapy for next assessments of the cost-effectiveness of ctDNA-guided strategies in selecting patients with stage II CC for adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
27. Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.
- Author
-
Mohamed, Yehia I., Lee, Sunyoung S., Demir, Tarik, Chamseddine, Shadi, Hu, Zishuo Ian, Xiao, Lianchun, Elsayes, Khaled, Morris, Jeffrey S., Wolff, Robert A., Hiatia, Rikita, Qayyum, Aliya, Rashid, Asif, Duda, Dan G., Yao, James C., LaPelusa, Michael, Koay, Eugene J., Mahvash, Armeen, Al Azzam, Ahmed, Dumbrava, Ecaterina E., and Hassan, Manal
- Subjects
- *
CIRCULATING tumor DNA , *CANCER prognosis , *PROGRESSION-free survival , *OVERALL survival , *HEPATOCELLULAR carcinoma - Abstract
BACKGROUND: Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC). OBJECTIVE: This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab. METHODS: We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions. RESULTS: Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p = 0.04). CONCLUSIONS: ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
28. Liquid biopsy for the management of NSCLC patients under osimertinib treatment.
- Author
-
Ntzifa, Aliki, Marras, Theodoros, Georgoulias, Vasilis, and Lianidou, Evi
- Subjects
- *
THERAPEUTIC use of antineoplastic agents , *MEDICAL protocols , *HETEROCYCLIC compounds , *PROTEIN-tyrosine kinase inhibitors , *MINIMALLY invasive procedures , *AMINES , *LUNG cancer , *GENETIC mutation , *EPIDERMAL growth factor receptors , *GENETIC testing ,BODY fluid examination - Abstract
Therapeutic management of NSCLC patients is quite challenging as they are mainly diagnosed at a late stage of disease, and they present a high heterogeneous molecular profile. Osimertinib changed the paradigm shift in treatment of EGFR mutant NSCLC patients achieving significantly better clinical outcomes. To date, osimertinib is successfully administered not only as first- or second-line treatment, but also as adjuvant treatment while its efficacy is currently investigated during neoadjuvant treatment or in stage III, unresectable EGFR mutant NSCLC patients. However, resistance to osimertinib may occur due to clonal evolution, under the pressure of the targeted therapy. The utilization of liquid biopsy as a minimally invasive tool provides insight into molecular heterogeneity of tumor clonal evolution and potent resistance mechanisms which may help to develop more suitable therapeutic approaches. Longitudinal monitoring of NSCLC patients through ctDNA or CTC analysis could reveal valuable information about clinical outcomes during osimertinib treatment. Therefore, several guidelines suggest that liquid biopsy in addition to tissue biopsy should be considered as a standard of care in the advanced NSCLC setting. This practice could significantly increase the number of NSCLC patients that will eventually benefit from targeted therapies, such as EGFR TKIs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
29. De-Escalation Strategies in HPV-Associated Oropharynx Cancer: A Historical Perspective with Future Direction.
- Author
-
Wu, Clinton, Kuzmin, Paulina, and Julian, Ricklie
- Subjects
- *
HEAD & neck cancer treatment , *PAPILLOMAVIRUS diseases , *SQUAMOUS cell carcinoma , *RADIOTHERAPY , *OROPHARYNGEAL cancer , *HEAD & neck cancer , *PAPILLOMAVIRUSES , *DNA , *TUMOR markers , *CANCER chemotherapy , *DISEASE complications - Abstract
Simple Summary: Patients with locoregional head and neck cancer often receive radiation and/or surgery with curative intent. Chemotherapy is often used as a radiation sensitizer or adjunctively to improve treatment effect. However, these modalities are often associated with significant and potentially debilitating adverse events, which negatively impacts quality of life. HPV-associated oropharyngeal head and neck cancer has been shown to be more responsive to treatment compared to HPV-negative disease. Therefore, various de-escalation strategies have been under investigation in hopes of optimizing therapeutic response while also minimizing toxicity from treatment. The incidence of HPV-related oropharyngeal cancers has increased in recent decades. While cure rates exceed those of HPV-negative head and neck cancers, both acute and long-term sequelae of chemotherapy, radiation and surgery have led to clinical investigation into de-escalation of treatment. De-escalation trials have sought to reduce long-term treatment-related morbidity by altering or omitting chemotherapy, reducing radiation, or incorporating less invasive surgical resection through transoral surgery. More recent approaches include the use of novel agents such as immunotherapy in place of cisplatin. With the advent of tumor-tissue-modified HPV DNA detection and monitoring in blood, new strategies incorporating this biomarker are being developed. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
30. Emerging Therapeutic Targets and Future Directions in Advanced Gastric Cancer: A Comprehensive Review.
- Author
-
Ratti, Margherita, Orlandi, Elena, Toscani, Ilaria, Vecchia, Stefano, Anselmi, Elisa, Hahne, Jens Claus, Ghidini, Michele, and Citterio, Chiara
- Subjects
- *
STOMACH tumors , *CANCER vaccines , *DNA , *CELLULAR signal transduction , *METASTASIS , *PROGRAMMED cell death 1 receptors , *PATHOGENESIS , *EPIDERMAL growth factor receptors , *CELL receptors - Abstract
Simple Summary: Metastatic gastric cancer (GC) remains a major clinical challenge due to scarce treatment options and an ominous prognosis, often diagnosed at later stages. Recent progress in identifying molecular targets and integrating immune checkpoint inhibitors with chemotherapy has transformed treatment strategies. The new classification of GC, based on immunologic and molecular markers, has drastically changed the therapeutic approach, focusing on personalized target-based treatments. This review summarizes molecular and immunological targets currently available and explores future approaches like circulating tumor DNA (ctDNA) monitoring, targeting fibroblast growth factor receptor (FGFR) and MET pathways, chimeric antigen receptor (CAR)-T cells, and cancer vaccines for their potential to improve understanding and treatment of this disease. Metastatic gastric cancer (GC) still represents a critical clinical challenge, with limited treatment options and a poor prognosis. Most patients are diagnosed at advanced stages, limiting the chances of surgery and cure. The identification of molecular targets and the possibility of combining immune checkpoint inhibitors with chemotherapy have recently reshaped the therapeutic landscape of metastatic gastric cancer. The new classification of gastric cancer, mainly based on immunologic and molecular criteria such as programmed cell death 1 (PD-1), microsatellite instability (MSI), and human epidermal growth factor receptor 2 (HER2), has made it possible to identify and differentiate patients who may benefit from immunotherapy, targeted therapy, or chemotherapy alone. All relevant and available molecular and immunological targets in clinical practice for the systemic treatment of this disease are presented. Particular attention is given to possible future approaches, including circulating tumor DNA (ctDNA) for therapeutic monitoring, new targeting agents against molecular pathways such as fibroblast growth factor receptor (FGFR) and MET, chimeric antigen receptor (CAR)-T cells, and cancer vaccines. This review aims to provide a comprehensive understanding of current targets in advanced gastric cancer and to offer valuable insights into future directions of research and clinical practice in this challenging disease. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. Use of Circulating Tumor DNA to Guide Decision-making in Adjuvant Colon Cancer.
- Author
-
Gottschalk, Zachary and Cohen, Stacey A.
- Abstract
Purpose of Review: The use of circulating tumor DNA (ctDNA) assays to guide clinical decision-making in early-stage colon cancer is an area of rapidly advancing active research. With assays clinically available, clinicians must be informed how to best use this novel tool to treat patients. Recent Findings: Recent observational and prospective studies have suggested that ctDNA has potential to guide clinical decision-making in early-stage colon cancer by detecting minimal residual disease (MRD) and predicting recurrence risks. MRD-negative patients may be able to de-escalate or forgo adjuvant chemotherapy (ACT) without compromising disease-free survival or overall survival, while MRD-positive patients may benefit significantly from ACT. Summary: Recent and ongoing studies have given reason for optimism about the future of ctDNA as a useful biomarker for clinicians treating early-stage colon cancer. Data thus far are mostly limited to observational studies; inconsistent results highlight the need for caution. As more evidence emerges, ctDNA may become standard of care for colon cancer patients. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
32. Pan-Canadian consensus recommendations for GIST management in high- and low-throughput centres across Canada.
- Author
-
Beecroft, J. Robert, Brar, Savtaj, Feng, Xiaolan, Hamilton, Trevor, Han-Lee, Cheng, Henning, Jan-Willem, Josephy, P. David, Khalili, Korosh, Ko, Yoo-Joung, Lemieux, Christopher, Liu, David M., MacDonald, D. Blair, Noujaim, Jonathan, Pollett, Aaron, Salawu, Abdulazeez, Saleh, Ramy, Smrke, Alannah, Warren, Blair E., Zbuk, Kevin, and Razak, Albiruni Abdul
- Abstract
Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours that originate from the interstitial cells of Cajal. GISTs are mainly driven by gain-of-function mutations in receptor tyrosine kinase or platelet-derived growth factor receptor alpha. Surgical resection is the only curative treatment for localized tumours and all currently approved medical GIST treatments are based on orally available tyrosine kinase inhibitors. Recent discoveries in the molecular and clinical features of GISTs have greatly impacted GIST management. Due to the provincially rather than nationally administered Canadian healthcare system, there have been inconsistencies in the treatment of GISTs across the country. Therefore, guidance on the latest knowledge, clinical management and treatment of GIST is needed to standardize the approach to GIST management nationwide. To establish pan-Canadian guidance, provide up-to-date data and harmonize the clinical practice of GIST management in high- and low-throughput centres across Canada; a panel of 20 physicians with extensive clinical experience in GIST management reviewed relevant literature. This included radiologists, pathologists, interventional radiologists, surgeons and medical oncologists across Canada. The structured literature focused on seven key domains: molecular profiling, radiological techniques/reporting, targeted localized therapy, intricacies of systemic treatments, emerging tests, multidisciplinary care and patient advocacy. This literature review, along with clinical expertise and opinion, was used to develop this concise and clinically relevant consensus paper to harmonize the knowledge and clinical practice on GIST management across Canada. The content presented here will help guide healthcare providers, especially in Canada, in terms of approaching and managing GIST. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
33. Evaluation of molecular residual disease in operable non-small cell lung cancer with gene fusions, MET exon skipping or de novo MET amplification.
- Author
-
Fu, Rui, Xiong, Yuanyuan, Cai, Miao, Li, Fang, Chen, Rongrong, Wu, Yilong, and Zhong, Wenzhao
- Abstract
Gene fusions and MET alterations are rare and difficult to detect in plasma samples. The clinical detection efficacy of molecular residual disease (MRD) based on circulating tumor DNA (ctDNA) in patients with non-small cell lung cancer (NSCLC) with these mutations remains unknown. This prospective, non-intervention study recruited 49 patients with operable NSCLC with actionable gene fusions (ALK, ROS1, RET, and FGFR1), MET exon 14 skipping or de novo MET amplification. We analyzed 43 tumor tissues and 111 serial perioperative plasma samples using 1021- and 338-gene panels, respectively. Detectable MRD correlated with a significantly higher recurrence rate (P < 0.001), yielding positive predictive values of 100% and 90.9%, and negative predictive values of 82.4% and 86.4% at landmark and longitudinal time points, respectively. Patients with detectable MRD showed reduced disease-free survival (DFS) compared to those with undetectable MRD (P < 0.001). Patients who harbored tissue-derived fusion/MET alterations in their MRD had reduced DFS compared to those who did not (P = 0.05). To our knowledge, this is the first comprehensive study on ctDNA-MRD clinical detection efficacy in operable NSCLC patients with gene fusions and MET alterations. Patients with detectable tissue-derived fusion/MET alterations in postoperative MRD had worse clinical outcomes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
34. ctDNA as an Adjunct to Posttreatment PET for Head and Neck Cancer Recurrence Risk Assessment.
- Author
-
Lele, Saudamini J., Adilbay, Dauren, Lewis, Ellen, Pang, John, Asarkar, Ameya A., and Nathan, Cherie‐Ann O.
- Abstract
Objective: Circulating tumor DNA (ctDNA) detection is an emerging technique that identifies minimal residual disease in patients with solid tumors. ctDNA can act as an adjunct method to help overcome the limitations of positron emission tomography (PET) and select patients who are at high risk for recurrence. Study Design: Retrospective Single Institutional Study. Setting: University Hospital Setting. Methods: Twenty‐nine patients who underwent definitive treatment for squamous cell carcinoma of the head and neck (HNSCC) from 8/2021 to 01/2023 had ctDNA levels analyzed at 1 to 3, 6, 9, and 12 months after definitive treatment. A personalized, tumor‐informed, multiplex polymerase chain reaction (PCR) next‐generation sequencing (NGS) assay was used to detect the ctDNA levels. The primary outcome was recurrence‐free probability (RFP), and the secondary outcomes were overall survival (OS), sensitivity, specificity, and the test's negative (NPV) and positive predictive values (PPV). Results: The median age of patients was 65 years (interquartile range: 56‐69), with majority being males (n = 22, 76%). The primary sites were larynx (n = 12), oropharynx (n = 10), and oral cavity (n = 6). Posttreatment ctDNA was detected in 7 patients, all of whom had disease recurrence. ctDNA detection after definitive treatment was associated with a higher risk of disease recurrence (hazard ratio: 9.94, 95% confidence interval: 1.56‐63.3, P =.015). ctDNA identified recurrence with 100% specificity and 78% sensitivity. The NPV and PPV were 91% and 100%. PET had 78% sensitivity but only 68% specificity with 86% NPV, and 54% PPV. Conclusion: Based on our data, ctDNA can be an excellent adjunct test for posttreatment PET and can help guide physicians in cases where PET results are inconclusive and difficult to interpret. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
35. Is ctDNA ready to outpace imaging in monitoring early and advanced breast cancer?
- Author
-
Foffano, Lorenzo, Vida, Riccardo, Piacentini, Alberto, Molteni, Elisabetta, Cucciniello, Linda, Da Ros, Lucia, Silvia, Buriolla, Cereser, Lorenzo, Roncato, Rossana, Gerratana, Lorenzo, and Puglisi, Fabio
- Subjects
METASTATIC breast cancer ,CIRCULATING tumor DNA ,INDIVIDUALIZED medicine ,BREAST cancer ,RADIOMICS - Abstract
Circulating tumor DNA (ctDNA) and radiological imaging are increasingly recognized as crucial elements in breast cancer management. While radiology remains the cornerstone for screening and monitoring, ctDNA holds distinctive advantages in anticipating diagnosis, recurrence, or progression, providing concurrent biological insights complementary to imaging results. This review delves into the current evidence on the synergistic relationship between ctDNA and imaging in breast cancer. It presents data on the clinical validity and utility of ctDNA in both early and advanced settings, providing insights into emerging liquid biopsy techniques like epigenetics and fragmentomics. Simultaneously, it explores the present and future landscape of imaging methodologies, particularly focusing on radiomics. Numerous are the current technical, strategic, and economic challenges preventing the clinical integration of ctDNA analysis in the breast cancer monitoring. Understanding these complexities and devising targeted strategies is pivotal to effectively embedding this methodology into personalized patient care. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
36. Circulating tumor DNA is a useful adjunct for Merkel cell carcinoma monitoring in the context of multiple metastatic malignancies
- Author
-
Daniel Wenzel, MD, Andrew M. Schuler, MD, David C. Smith, MD, Joseph R. Evans, MD, PhD, Kelly L. Harms, MD, PhD, and Elisabeth A. Pedersen, MD, PhD
- Subjects
ctDNA ,cutaneous oncology ,dermatology ,Merkel cell carcinoma ,oncology ,Dermatology ,RL1-803 - Published
- 2024
- Full Text
- View/download PDF
37. Clinical utility of ctDNA by amplicon based next generation sequencing in first line non small cell lung cancer patients
- Author
-
Valerio Gristina, Tancredi Didier Bazan Russo, Nadia Barraco, Andrea Gottardo, Francesco Pepe, Gianluca Russo, Fabio Fulfaro, Lorena Incorvaia, Giuseppe Badalamenti, Giancarlo Troncone, Umberto Malapelle, Antonio Russo, Viviana Bazan, and Antonio Galvano
- Subjects
NSCLC ,Liquid biopsy ,CtDNA ,NGS ,Monitoring ,Medicine ,Science - Abstract
Abstract The assessment of ctDNA has emerged as a minimally invasive avenue for molecular diagnosis and real-time tracking of tumor progression in NSCLC. However, the evaluation of ctDNA by amplicon-based NGS has been not endorsed by all the healthcare systems and remains to be fully integrated into clinical routine practice. To compare tissue single-gene with plasma multiplexed testing, we retrospectively evaluated 120 plasma samples from 12 consecutive patients with advanced non-squamous NSCLC who were part of a prospective study enrolling treatment-naïve patients and in which tissue samples were evaluated using a single-gene testing approach. While the plasma ctDNA detection of EGFR and BRAF mutations had an acceptable level of concordance with the archival tissue (85%), discordance was seen in all the patients in whom ALK alterations were only detected in tissue samples. Among six responders and six non-responders, early ctDNA mutant allelic frequency (MAF) reduction seemed to predict radiologic responses and longer survival, whereas increasing MAF values with the emergence of co-mutations like BRAFV600E, KRASG12V or TP53M237I seemed to be an early indicator of molecular and radiologic progression. This report using an amplicon-based NGS assay on ctDNA underscores the real-life need for plasma and tissue genotyping as complementary tools in the diagnostic and therapeutic decision-making process.
- Published
- 2024
- Full Text
- View/download PDF
38. Benchmarking UMI-aware and standard variant callers for low frequency ctDNA variant detection
- Author
-
Rugare Maruzani, Liam Brierley, Andrea Jorgensen, and Anna Fowler
- Subjects
Variant calling ,ctDNA ,Next generation sequencing ,Cancer ,Biotechnology ,TP248.13-248.65 ,Genetics ,QH426-470 - Abstract
Abstract Background Circulating tumour DNA (ctDNA) is a subset of cell free DNA (cfDNA) released by tumour cells into the bloodstream. Circulating tumour DNA has shown great potential as a biomarker to inform treatment in cancer patients. Collecting ctDNA is minimally invasive and reflects the entire genetic makeup of a patient’s cancer. ctDNA variants in NGS data can be difficult to distinguish from sequencing and PCR artefacts due to low abundance, particularly in the early stages of cancer. Unique Molecular Identifiers (UMIs) are short sequences ligated to the sequencing library before amplification. These sequences are useful for filtering out low frequency artefacts. The utility of ctDNA as a cancer biomarker depends on accurate detection of cancer variants. Results In this study, we benchmarked six variant calling tools, including two UMI-aware callers for their ability to call ctDNA variants. The standard variant callers tested included Mutect2, bcftools, LoFreq and FreeBayes. The UMI-aware variant callers benchmarked were UMI-VarCal and UMIErrorCorrect. We used both datasets with known variants spiked in at low frequencies, and datasets containing ctDNA, and generated synthetic UMI sequences for these datasets. Variant callers displayed different preferences for sensitivity and specificity. Mutect2 showed high sensitivity, while returning more privately called variants than any other caller in data without synthetic UMIs – an indicator of false positive variant discovery. In data encoded with synthetic UMIs, UMI-VarCal detected fewer putative false positive variants than all other callers in synthetic datasets. Mutect2 showed a balance between high sensitivity and specificity in data encoded with synthetic UMIs. Conclusions Our results indicate UMI-aware variant callers have potential to improve sensitivity and specificity in calling low frequency ctDNA variants over standard variant calling tools. There is a growing need for further development of UMI-aware variant calling tools if effective early detection methods for cancer using ctDNA samples are to be realised.
- Published
- 2024
- Full Text
- View/download PDF
39. Focal Update on Immunotherapy and Liver Transplantation in the Era of Transplant Oncology
- Author
-
Maen Abdelrahim, Abdullah Esmail, Taizo Hibi, and Vincenzo Mazzaferro
- Subjects
immunotherapy ,liver transplantation ,transplant oncology ,ctDNA ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Transplant oncology is an expanding area of cancer therapy that specifically emphasizes the use of liver transplantation (LT) as the preferred treatment for patients with manageable, but unresectable, tumors. The management and optimization of overall survival strategies, accompanied by an arguably decent quality of life, have been at the forefront of liver oncology treatment, as a plurality of all primary liver cancers are identified as either hepatocellular carcinoma (HCC) or cholangiocarcinoma (CCA), which are classified as highly aggressive malignancies and frequently remain asymptomatic until they progress to advanced stages, rendering curative procedures, such as resection, impractical. This has led to an increase in utilization of neoadjuvant interventions conducted prior to surgery, which has yielded favorable outcomes. Though this treatment modality has prompted further investigations into the efficacy of immune checkpoint inhibitors (ICPIs) as standalone treatments and in combination with locoregional treatments (LRTs) to bridge more patients into curative eligibility. This multidisciplinary methodology and treatment planning has seen multiple successful trials of immunotherapy regimes and combinate treatments, setting the groundwork for increasing eligibility through downstaging and “bridging” previously ineligible patients within stringent LT criteria. Surveillance after LT is a crucial component of transplant oncology. The emergence of circulating tumor DNA (ctDNA) has provided a novel approach to identifying the recurrence of cancer in its early stages. Recent research has focused on liquid biopsy, a technique that effectively identifies the dynamics of cancer. This is another innovation to demonstrate the rate at which transplant oncology is rapidly advancing, making the focus of care feel disorienting. Modalities of care are constantly evolving, but when a field is changing as rapidly as this one, it is imperative to reorient to the data and the needs of the patients. In this commentary, we reflect on the update’s utilization of ICPIs in neoadjuvant settings as well as the updates on the utilization of liquid biopsy in post-LT follow-up surveillance.
- Published
- 2024
- Full Text
- View/download PDF
40. Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA
- Author
-
Jennifer H. Chen, Sridevi Addanki, Dhruvajyoti Roy, Roland Bassett, Ekaterina Kalashnikova, Erik Spickard, Henry M. Kuerer, Salyna Meas, Vanessa N. Sarli, Anil Korkut, Jason B. White, Gaiane M. Rauch, Debu Tripathy, Banu K. Arun, Carlos H. Barcenas, Clinton Yam, Himanshu Sethi, Angel A. Rodriguez, Minetta C. Liu, Stacy L. Moulder, and Anthony Lucci
- Subjects
Liquid biopsy ,ctDNA ,CTC ,Triple negative breast cancer ,Liquid biopsy in neoadjuvant setting ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC). Methods Patients with TNBC were enrolled between 2017–2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (SignateraTM, Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher’s exact tests were used for comparisons between groups and Kaplan–Meier analysis used for survival outcomes. Results In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively). Conclusions Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.
- Published
- 2024
- Full Text
- View/download PDF
41. Additional considerations before using a ctDNA-guided approach for informing adjuvant chemotherapy in colorectal cancer.
- Author
-
Olivier, Timothée, Haslam, Alyson, and Prasad, Vinay
- Subjects
Adjuvant therapy ,Colon cancer ,Evidence-based medicine ,Molecular test ,Non-inferiority ,Oncology ,ctDNA ,Humans ,Chemotherapy ,Adjuvant ,Adjuvants ,Immunologic ,Circulating Tumor DNA ,Oxaliplatin ,Colorectal Neoplasms - Abstract
BACKGROUND: The DYNAMIC trial investigated the use of circulating tumor DNA (ctDNA) to guide adjuvant treatment decisions in stage II colon cancer. Despite the DYNAMIC trials assertion that a ctDNA-guided approach could minimize the use of adjuvant treatment without compromising recurrence-free survival (RFS), we raised concerns regarding the trials methodology and the practical implications of its findings in a Debate article. Here, we expand upon these concerns in a response to a correspondence by the authors of the DYNAMIC trial. MAIN BODY: We dispute the choice of a large non-inferiority margin in the DYNAMIC trial, simply because an 8.5 percentage points decrease in recurrence-free survival could result in significant harm to patients. We challenge the authors comparisons of the DYNAMIC trial outcomes with observational studies. Such comparison is subject to selection bias and changes over time that limit their relevance. The prognostic role of ctDNA do not automatically imply that more treatment in patients with ctDNA positivity would improve outcomes, which we highlight. In real-world settings, we anticipate a potential rise in chemotherapy use due to clinicians utilizing ctDNA alongside existing clinicopathologic factors, rather than using ctDNA as an entire replacement. Lastly, a key concern in DYNAMIC was an 350% higher use of oxaliplatin in the ctDNA arm compared with standard management (9.5% versus 2.7%, respectively), which poses a risk for long-term neuropathy. CONCLUSION: We look forward improvements in patient selection in the adjuvant setting, but we maintain our reservations about the DYNAMIC trial and the real-life implementation of its results. As an alternative to exploring de-escalation strategies with large margins non-inferiority trials, we propose that superiority trials in stage II patients could be a more effective strategy.
- Published
- 2023
42. Application of liquid biopsy in lung cancer management
- Author
-
Shraddhanjali Satapathy, Balamurugan Thirunavukkarasu, and Deepali Jain
- Subjects
cfdna ,ctc ,ctdna ,extracellular vesicle ,fragmentosome ,liquid biopsy ,lung adenocarcinoma ,Pathology ,RB1-214 ,Microbiology ,QR1-502 - Abstract
Current advances in the understanding of the lung cancer landscape have drastically changed the approach to treating a patient with lung carcinoma. The field has progressed from analyzing single gene to using advanced techniques like next-generation sequencing and microarray technology. While a tumor tissue sample is considered the gold standard, it has several limitations. The limitations of invasive procedures, long processing periods, inaccessibility, and sample inadequacy are being addressed by sampling biofluids, termed ‘liquid biopsy,’ which offers a less invasive and more accessible way to obtain tumor-related information. Liquid biopsy has transformed the care of lung cancer patients by directly targeting somatic alterations from tumors. This article provides insights into the biology, technical aspects, limitations, and practical applications of ‘liquid biopsy,’ focusing on cell-free DNA and circulating tumor DNA in the context of lung cancer.
- Published
- 2024
- Full Text
- View/download PDF
43. Quantification method of ctDNA using cell-free DNA methylation profile for noninvasive screening and monitoring of colon cancer
- Author
-
Hyojung Ryu, Ji-Hoon Kim, Yeo Jin Kim, Hahyeon Jeon, Byoung-Chul Kim, Yeonsu Jeon, Yeonkyung Kim, Hyebin Bak, Younghui Kang, Changjae Kim, Hyojin Um, Ji-Hye Ahn, Hwi Hyun, Byung Chul Kim, Inho Song, Sungwon Jeon, Jong Bhak, and Eon Chul Han
- Subjects
Colon cancer ,ctDNA ,Epigenetic diagnosis ,Liquid biopsy ,Postoperative monitoring ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. Results We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. Conclusions This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer.
- Published
- 2024
- Full Text
- View/download PDF
44. Novel liquid biopsy CNV biomarkers in malignant melanoma
- Author
-
E. Lukacova, Z. Hanzlikova, P. Podlesnyi, T. Sedlackova, T. Szemes, M. Grendar, M. Samec, T. Hurtova, B. Malicherova, K. Leskova, J. Budis, and T. Burjanivova
- Subjects
Melanoma ,Liquid biopsy ,ctDNA ,Biomarker ,ddPCR ,lcWGS ,Medicine ,Science - Abstract
Abstract Malignant melanoma (MM) is known for its abundance of genetic alterations and a tendency for rapid metastasizing. Identification of novel plasma biomarkers may enhance non-invasive diagnostics and disease monitoring. Initially, we examined copy number variations (CNV) in CDK genes (CDKN2A, CDKN2B, CDK4) using MLPA (gDNA) and ddPCR (ctDNA) analysis. Subsequently, low-coverage whole genome sequencing (lcWGS) was used to identify the most common CNV in plasma samples, followed by ddPCR verification of chosen biomarkers. CNV alterations in CDK genes were identified in 33.3% of FFPE samples (Clark IV, V only). Detection of the same genes in MM plasma showed no significance, neither compared to healthy plasmas nor between pre- versus post-surgery plasma. Sequencing data showed the most common CNV occurring in 6q27, 4p16.1, 10p15.3, 10q22.3, 13q34, 18q23, 20q11.21-q13.12 and 22q13.33. CNV in four chosen genes (KIF25, E2F1, DIP2C and TFG) were verified by ddPCR using 2 models of interpretation. Model 1 was concordant with lcWGS results in 54% of samples, for model 2 it was 46%. Although CDK genes have not been proven to be suitable CNV liquid biopsy biomarkers, lcWGS defined the most frequently affected chromosomal regions by CNV. Among chosen genes, DIP2C demonstrated a potential for further analysis.
- Published
- 2024
- Full Text
- View/download PDF
45. A Locally Advanced NSCLC Patient Harboring a Rare KIF13A-RET Fusion Benefited from Pralsetinib: A Case Report
- Author
-
Zenghao Chang, Tengfei Zhu, Hao Jiang, Wei Ou, and Siyu Wang
- Subjects
RET fusion ,pralsetinib ,adjuvant treatment ,ctDNA ,NSCLC ,case report ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The application of adjuvant treatment has significantly enhanced the survival of patients with resectable non-small cell lung cancer (NSCLC) carrying driver gene mutations. However, adjuvant-targeted therapy remains controversial for some NSCLC patients carrying rare gene mutations such as RET, as there is currently a lack of confirmed randomized controlled trials demonstrating efficacy. In this report, we describe the case of a 58-year-old man with stage IIIA NSCLC who underwent complete lobectomy with selective lymph node dissection. Postoperative next-generation sequencing revealed that the patient harbored a rare KIF13A-RET fusion. The patient elected to receive adjuvant treatment with pralsetinib monotherapy and underwent serial circulating tumor DNA (ctDNA) monitoring after surgery. During follow-up, despite experiencing dose reduction and irregular medication adherence, the patient still achieved a satisfactory disease-free survival (DFS) of 27 months. Furthermore, ctDNA predicted tumor recurrence 4 months earlier than imaging techniques. The addition of bevacizumab to the original regimen upon recurrence continued to be beneficial. Pralsetinib demonstrated promising efficacy as adjuvant therapy, while ctDNA analysis offered a valuable tool for early detection of tumor recurrence. By leveraging targeted therapies and innovative monitoring techniques, we aim to improve outcomes and quality of life for NSCLC patients in the future.
- Published
- 2024
- Full Text
- View/download PDF
46. Deep learning model integrating cfDNA methylation and fragment size profiles for lung cancer diagnosis
- Author
-
Minjung Kim, Juntae Park, Seonghee Oh, Byeong-Ho Jeong, Yuree Byun, Sun Hye Shin, Yunjoo Im, Jong Ho Cho, and Eun-Hae Cho
- Subjects
Lung cancer ,ctDNA ,Methylation ,MeDIP-seq ,EM-seq ,Medicine ,Science - Abstract
Abstract Detecting aberrant cell-free DNA (cfDNA) methylation is a promising strategy for lung cancer diagnosis. In this study, our aim is to identify methylation markers to distinguish patients with lung cancer from healthy individuals. Additionally, we sought to develop a deep learning model incorporating cfDNA methylation and fragment size profiles. To achieve this, we utilized methylation data collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Then we generated methylated DNA immunoprecipitation sequencing and genome-wide Enzymatic Methyl-seq (EM-seq) form lung cancer tissue and plasma. Using these data, we selected 366 methylation markers. A targeted EM-seq panel was designed using the selected markers, and 142 lung cancer and 56 healthy samples were produced with the panel. Additionally, cfDNA samples from healthy individuals and lung cancer patients were diluted to evaluate sensitivity. Its lung cancer detection performance reached an accuracy of 81.5% and an area under the receiver operating characteristic curve of 0.87. In the serial dilution experiment, we achieved tumor fraction detection of 1% at 98% specificity and 0.1% at 80% specificity. In conclusion, we successfully developed and validated a combination of methylation panel and a deep learning model that can distinguish between patients with lung cancer and healthy individuals.
- Published
- 2024
- Full Text
- View/download PDF
47. The prognostic role of circulating tumor DNA across breast cancer molecular subtypes: A systematic review and meta-analysis
- Author
-
Nana Guo, Qingxin Zhou, Meng Zhang, Xiaowei Chen, Baoqi Zeng, Shanshan Wu, Hongmei Zeng, Mopei Wang, Fei Ma, and Feng Sun
- Subjects
ctDNA ,Breast cancer ,Molecular subtype ,RFS ,OS ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle. Materials and methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS). Results: A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery. Conclusions: ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.
- Published
- 2024
- Full Text
- View/download PDF
48. Concept and feasibility of the Augsburg Longitudinal Plasma Study (ALPS) – a prospective trial for comprehensive liquid biopsy-based longitudinal monitoring of solid cancer patients
- Author
-
Sommer Sebastian, Schmutz Maximilian, Hildebrand Kathrin, Schiwitza Annett, Benedikt Selinah, Eberle Maria, Mögele Tatiana, Sultan Aziz, Reichl Lena, Campillo Maria, Uhrmacher Luise, Nikolic Ana Antic, Bundschuh Ralph, Lapa Constantin, Kuhlen Michaela, Dintner Sebastian, Langer Angela, Märkl Bruno, Wendler Thomas, Tehlan Kartikay, Kröncke Thomas, Wahle Maria, Mann Matthias, Casadei Nicolas, Pogoda Michaela, Hummler Simone, Sax Irmengard, Schlesner Matthias, Kubuschok Boris, Trepel Martin, and Claus Rainer
- Subjects
liquid biopsy ,ctdna ,longitudinal profiling ,clonal evolution ,spatial heterogeneity ,translational research ,Medical technology ,R855-855.5 - Abstract
Liquid biopsy (LBx) provides diagnostic, prognostic and predictive insights for malignant diseases and offers promising applications regarding tumor burden, tumor heterogeneity and clonal evolution.
- Published
- 2024
- Full Text
- View/download PDF
49. Personalized, tumor‐informed, circulating tumor DNA assay for detecting minimal residual disease in non‐small cell lung cancer patients receiving curative treatments
- Author
-
Youjin Oh, Sung Mi Yoon, Jeeyeon Lee, Joo Hee Park, Soowon Lee, Timothy Hong, Liam Il‐young Chung, Sumedha Sudhaman, Timothy Riddell, Charuta C. Palsuledesai, Michael Krainock, Minetta C. Liu, and Young Kwang Chae
- Subjects
biomarker ,ctDNA ,lung cancer ,molecular residual disease ,prognosis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Circulating tumor DNA (ctDNA) has emerged as a prognostic and predictive biomarker for detection of minimal residual disease (MRD), monitoring treatment response, and early detection of recurrence in cancer patients. In this study, we explored the utility of ctDNA‐based MRD detection to predict recurrence in a real‐world cohort of primarily early‐stage non‐small cell lung cancer (NSCLC) patients treated with curative intent. Methods Longitudinal plasma samples were collected post curative‐intent treatment from 36 patients with stage I–IV NSCLC. A personalized, tumor‐informed assay was used to detect and quantify ctDNA in plasma samples. Results Of the 24 patients with plasma samples available during the MRD window (within 6 months of curative surgery and before adjuvant therapy), ctDNA was detectable in two patients. Patients with ctDNA‐positivity during the MRD window were 15 times more likely to recur compared to ctDNA‐negative patients (HR: 15.0, 95% CI: 1.0–253.0, p = 0.010). At any time post‐curative intent treatment, ctDNA‐positivity was associated with significantly poorer recurrence‐free survival compared to persistently ctDNA‐negative patients (p
- Published
- 2024
- Full Text
- View/download PDF
50. Quantification method of ctDNA using cell-free DNA methylation profile for noninvasive screening and monitoring of colon cancer.
- Author
-
Ryu, Hyojung, Kim, Ji-Hoon, Kim, Yeo Jin, Jeon, Hahyeon, Kim, Byoung-Chul, Jeon, Yeonsu, Kim, Yeonkyung, Bak, Hyebin, Kang, Younghui, Kim, Changjae, Um, Hyojin, Ahn, Ji-Hye, Hyun, Hwi, Kim, Byung Chul, Song, Inho, Jeon, Sungwon, Bhak, Jong, and Han, Eon Chul
- Subjects
- *
CELL-free DNA , *COLON cancer , *DNA methylation , *CIRCULATING tumor DNA , *MEDICAL screening , *CANCER patients - Abstract
Background: Colon cancer ranks as the second most lethal form of cancer globally. In recent years, there has been active investigation into using the methylation profile of circulating tumor DNA (ctDNA), derived from blood, as a promising indicator for diagnosing and monitoring colon cancer. Results: We propose a liquid biopsy-based epigenetic method developed by utilizing 49 patients and 260 healthy controls methylation profile data to screen and monitor colon cancer. Our method initially identified 901 colon cancer-specific hypermethylated (CaSH) regions in the tissues of the 49 cancer patients. We then used these CaSH regions to accurately quantify the amount of circulating tumor DNA (ctDNA) in the blood samples of these same patients, utilizing cell-free DNA methylation profiles. Notably, the methylation profiles of ctDNA in the blood exhibited high sensitivity (82%) and specificity (93%) in distinguishing patients with colon cancer from the control group, with an area under the curve of 0.903. Furthermore, we confirm that our method for ctDNA quantification is effective for monitoring cancer patients and can serve as a valuable tool for postoperative prognosis. Conclusions: This study demonstrated a successful application of the quantification of ctDNA among cfDNA using the original cancer tissue-derived CaSH region for screening and monitoring colon cancer. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.